Forget G, Lacroix M J, Calvert R, Sirois P
Inflammation. 1984 Jun;8(2):123-41. doi: 10.1007/BF00916089.
Chrysotile asbestos has been implicated with lung disorders, notably fibrotic lesions and cancer. In vitro, chrysotile fibers are cytotoxic to lung macrophages and stimulate the release of inflammatory mediators. Reports to the effect that chemical modifications of asbestos fibers reduce their cytotoxic and inflammatory potential initiated the present study of three fiber modifications. The cytotoxic and inflammatory effects of magnesium-leached chrysotile, POCL3-treated chrysotile, and CaO-treated chrysotile were studied in a perifused rat alveolar macrophage culture system, relative to untreated fibers. Natural Canadian chrysotile (UICC "B") caused dose-dependent cell mortality and clumping. The release of beta-glucuronidase (beta-Glu), a lysosomal enzyme, was also dose dependent. Rhodesian chrysotile (UICC "A") caused similar cytotoxic and inflammatory effects. However, magnesium-leached chrysotile was less cytotoxic (39% less) and had a lesser clumping capacity (31% less) than untreated chrysotile. Total secretion of beta-Glu elicited by magnesium-leached chrysotile was reduced by 43% from the untreated sample, but kinetic monitoring indicates that this reduction in inflammatory potential is only significant during the first 12 h of an 18-h culture period. POCl3 treatment of chrysotile fibers produced differing effects depending on the length of the fibers under study. Treating fibers with a mean length of 8 micron produced a secretion pattern similar to that produced by acid leaching. The total output for the treated sample was 44% lower than with untreated chrysotile; the difference was only significant during the first 12 h of perifusion. Cell mortality and aggregation were not reduced in any important way with POCl3 treatment of these longer fibers. When ultra-short fibers (mean length = 0.8 micron) were treated with POCl3, the total decrease in beta-Glu output was equal to 41%, and the release of enzyme was significantly lower during the whole 18-h experiment. Cell aggregation was not appreciably affected, but cell mortality was significantly lower than for untreated fibers. CaO treatment did not alter the cytotoxic (cell death and aggregation) or inflammatory (beta-Glu release) effects of chrysotile asbestos. These results suggest that chemical modifications affecting the integrity of the surface magnesium and/or the polarity of the surface charge of chrysotile can reduce to some extent the cytotoxic and inflammatory properties of this type of asbestos.
温石棉与肺部疾病有关，尤其是纤维化病变和癌症。在体外，温石棉纤维对肺巨噬细胞具有细胞毒性，并刺激炎症介质的释放。有报道称石棉纤维的化学修饰可降低其细胞毒性和炎症潜能，因此开展了本项对三种纤维修饰的研究。在灌流大鼠肺泡巨噬细胞培养系统中，研究了脱镁温石棉、POCL3处理的温石棉和CaO处理的温石棉相对于未处理纤维的细胞毒性和炎症作用。天然加拿大温石棉（UICC “B”）可导致剂量依赖性细胞死亡和聚集。溶酶体酶β-葡萄糖醛酸酶（β-Glu）的释放也呈剂量依赖性。罗德西亚温石棉（UICC “A”）具有类似的细胞毒性和炎症作用。然而，脱镁温石棉的细胞毒性比未处理的温石棉低（低39%），聚集能力也较弱（低31%）。脱镁温石棉引起的β-Glu总分泌量比未处理样品减少了43%，但动力学监测表明，在18小时培养期的前12小时内，这种炎症潜能的降低才显著。POCl3处理温石棉纤维产生的效果取决于所研究纤维的长度。处理平均长度为8微米的纤维产生的分泌模式与酸浸产生的模式相似。处理后样品的总分泌量比未处理的温石棉低44%；差异仅在灌流的前12小时显著。用POCl3处理这些较长纤维，细胞死亡率和聚集并未以任何重要方式降低。当用POCl3处理超短纤维（平均长度 = 0.8微米）时，β-Glu分泌量的总减少量等于41%，并且在整个18小时实验中酶的释放显著较低。细胞聚集没有受到明显影响，但细胞死亡率显著低于未处理的纤维。CaO处理并未改变温石棉的细胞毒性（细胞死亡和聚集）或炎症作用（β-Glu释放）。这些结果表明，影响温石棉表面镁完整性和/或表面电荷极性的化学修饰可在一定程度上降低这类石棉的细胞毒性和炎症特性。
